Multi-Omic Analysis Identifies Epigenetic Evolution In Relapsed Acute Myeloid Leukemia

Introduction: Acute myeloid leukemia (AML) is associated with a poor prognosis even with aggressive treatments including high dose chemotherapy. While most patients enter clinical remission, these remissions are often short-lived leading to chemotherapy-resistant relapsed disease that accounts for the majority of deaths. We undertook a meta-analysis of published datasets consisting of 142 genotyped paired diagnosis-relapse AML samples to understand the genetic evolution of AML between the two disease states. This analysis determined that a plurality of cases exhibited the same mutations at diagnosis and relapse, and that genetically stable clones were associated with an increased probability of relapse. The finding that many cases exhibited no clonal genetic evolution upon relapse, yet exhibited chemotherapy resistance, lead us to hypothesize that epigenetic evolution plays a significant role in AML relapse. Here, our objective was to investigate the epigenetic evolution and cis and trans regulatory elements that correlate with AML relapse.